Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants
Accumulation of δ-aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to rever...
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2003
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v35_n1_p1_Juknat http://hdl.handle.net/20.500.12110/paper_07423098_v35_n1_p1_Juknat |
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paper:paper_07423098_v35_n1_p1_Juknat2023-06-08T15:44:43Z Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants Juknat, Adela Ana Kotler, Mónica Lidia Quaglino, Ana δ-aminolevulinic acid Antioxidant enzymes Astrocyte Glutathione Melatonin Necrosis Reactive oxygen species aminolevulinic acid antioxidant caspase 3 catalase glutathione lipocortin 5 malonaldehyde melatonin porphobilinogen deaminase porphyrin propidium iodide superoxide dismutase animal cell animal tissue apoptosis article astrocyte bioaccumulation biosynthesis cell damage cell death cell membrane cell protection cell structure cell viability controlled study enzyme activity incubation time lipid peroxidation mouse nonhuman Aminolevulinic Acid Animals Antioxidants Astrocytes Cell Death Lipid Peroxidation Melatonin Mice Photosensitizing Agents Porphyrins Accumulation of δ-aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA-promoted damage, by incubating mouse astrocytes with 1.0 mM ALA for different times (1-4 hr) in the presence of melatonin (2.5 mM), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mM). The defined relative index [(malondialdehyde levels/accumulated ALA) x 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA-promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3-like activity was detected. These findings provide the first experimental evidence of the involvement of ALA-promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology. Fil:Juknat, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kotler, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v35_n1_p1_Juknat http://hdl.handle.net/20.500.12110/paper_07423098_v35_n1_p1_Juknat |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
δ-aminolevulinic acid Antioxidant enzymes Astrocyte Glutathione Melatonin Necrosis Reactive oxygen species aminolevulinic acid antioxidant caspase 3 catalase glutathione lipocortin 5 malonaldehyde melatonin porphobilinogen deaminase porphyrin propidium iodide superoxide dismutase animal cell animal tissue apoptosis article astrocyte bioaccumulation biosynthesis cell damage cell death cell membrane cell protection cell structure cell viability controlled study enzyme activity incubation time lipid peroxidation mouse nonhuman Aminolevulinic Acid Animals Antioxidants Astrocytes Cell Death Lipid Peroxidation Melatonin Mice Photosensitizing Agents Porphyrins |
| spellingShingle |
δ-aminolevulinic acid Antioxidant enzymes Astrocyte Glutathione Melatonin Necrosis Reactive oxygen species aminolevulinic acid antioxidant caspase 3 catalase glutathione lipocortin 5 malonaldehyde melatonin porphobilinogen deaminase porphyrin propidium iodide superoxide dismutase animal cell animal tissue apoptosis article astrocyte bioaccumulation biosynthesis cell damage cell death cell membrane cell protection cell structure cell viability controlled study enzyme activity incubation time lipid peroxidation mouse nonhuman Aminolevulinic Acid Animals Antioxidants Astrocytes Cell Death Lipid Peroxidation Melatonin Mice Photosensitizing Agents Porphyrins Juknat, Adela Ana Kotler, Mónica Lidia Quaglino, Ana Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| topic_facet |
δ-aminolevulinic acid Antioxidant enzymes Astrocyte Glutathione Melatonin Necrosis Reactive oxygen species aminolevulinic acid antioxidant caspase 3 catalase glutathione lipocortin 5 malonaldehyde melatonin porphobilinogen deaminase porphyrin propidium iodide superoxide dismutase animal cell animal tissue apoptosis article astrocyte bioaccumulation biosynthesis cell damage cell death cell membrane cell protection cell structure cell viability controlled study enzyme activity incubation time lipid peroxidation mouse nonhuman Aminolevulinic Acid Animals Antioxidants Astrocytes Cell Death Lipid Peroxidation Melatonin Mice Photosensitizing Agents Porphyrins |
| description |
Accumulation of δ-aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria (AIP), is the origin of an endogenous source of reactive oxygen species (ROS), which can exert oxidative damage to cell structures. In the present work we examined the ability of different antioxidants to revert ALA-promoted damage, by incubating mouse astrocytes with 1.0 mM ALA for different times (1-4 hr) in the presence of melatonin (2.5 mM), superoxide dismutase (25 units/mL), catalase (200 units/mL) or glutathione (0.5 mM). The defined relative index [(malondialdehyde levels/accumulated ALA) x 100], decreases with incubation time, reaching values of 76% for melatonin and showing that the different antioxidants tested can protect astrocytes against ALA-promoted lipid peroxidation. Concerning porphyrin biosynthesis, no effect was observed with catalase and superoxide dismutase whereas increases of 57 and 87% were obtained with glutathione and melatonin, respectively, indicating that these antioxidants may prevent the oxidation of porphobilinogen deaminase, reactivating so that the AIP genetically reduced enzyme. Here we showed that ALA induces cell death displaying a pattern of necrosis. This pattern was revealed by loss of cell membrane integrity, marked nuclear swelling and double labeling with annexin V and propidium iodide. In addition, no caspase 3-like activity was detected. These findings provide the first experimental evidence of the involvement of ALA-promoted ROS in the damage of proteins related to porphyrin biosynthesis and the induction of necrotic cell death in astrocytes. Interestingly, melatonin decreases the number of enlarged nuclei and shows a protective effect on cellular morphology. |
| author |
Juknat, Adela Ana Kotler, Mónica Lidia Quaglino, Ana |
| author_facet |
Juknat, Adela Ana Kotler, Mónica Lidia Quaglino, Ana |
| author_sort |
Juknat, Adela Ana |
| title |
Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| title_short |
Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| title_full |
Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| title_fullStr |
Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| title_full_unstemmed |
Necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. Protective role of melatonin and other antioxidants |
| title_sort |
necrotic cell death induced by δ-aminolevulinic acid in mouse astrocytes. protective role of melatonin and other antioxidants |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v35_n1_p1_Juknat http://hdl.handle.net/20.500.12110/paper_07423098_v35_n1_p1_Juknat |
| work_keys_str_mv |
AT juknatadelaana necroticcelldeathinducedbydaminolevulinicacidinmouseastrocytesprotectiveroleofmelatoninandotherantioxidants AT kotlermonicalidia necroticcelldeathinducedbydaminolevulinicacidinmouseastrocytesprotectiveroleofmelatoninandotherantioxidants AT quaglinoana necroticcelldeathinducedbydaminolevulinicacidinmouseastrocytesprotectiveroleofmelatoninandotherantioxidants |
| _version_ |
1768546401969504256 |